At the collision moment, a driver’s lower extremity will be in different foot position, which leads to the different posture of the lower extremity with various muscle activations. These will affect the driver’s injury during collision, so it is necessary to investigate further. A simulated collision scene was constructed, and 20 participants (10 male and 10 female) were recruited for the test in a driving simulator. The braking posture and muscle activation of eight major muscles of driver’s lower extremity (both legs) were measured. The muscle activations in different postures were then analyzed. At the collision moment, the right leg was possible to be on the brake (male, 40%; female, 45%), in the air (male, 27.5%; female, 37.5%) or even on the accelerator (male, 25%; female, 12.5%). The left leg was on the floor all along. Muscle activation of gastrocnemius, vastus medialis and vastus lateralis of right legs of male drivers in brake pedal region were significantly larger compared to the other positions, and that of soleus and hamstrings were significantly greater compared to air region. Gluteus maximus showed small muscle activation all along (<10%). Right leg showed larger muscle activation than left leg in the air and brake pedal region for most muscles of both genders (except for gluteus maximus). The right and left legs were in different postures at the collision moment, which affects the muscle activation. Differences were also found between muscles and genders. Therefore, muscle activation should be precisely measured, and the influence of these factors should be considered in the future injury analysis of lower extremity.